Q&A: How can novel antibiotics help combat antimicrobial resistance?
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Key takeaways:
- Antimicrobial resistance is responsible for 4.95 million deaths each year globally.
- Improved incentivization and funding for pharmaceutical companies could help bolster interest in antibiotic development.
PHILADELPHIA — At this year’s World Anti-Microbial Resistance Congress, Ricardo Chaves, MD, PhD, the executive medical director of clinical development at Debiopharm, moderated a panel on novel antibiotics.
During the panel, the experts discussed microbiome-sparing antibiotics, as well as the potential need for new pathways in regulatory approval and reimbursement.
We spoke further with Chaves about how these novel antibiotics could help fight antimicrobial resistance (AMR), what is currently in the pipeline and what could be done to help bolster the development of new antibiotics.
Healio: How can novel antibiotics help combat AMR?
Chaves: Globally, AMR is responsible for 4.95 million deaths each year, with low- and mid-income countries accounting for the majority of those fatalities. It might come as a surprise to many that today nearly all classes of antibiotics are becoming ineffective or at least significantly less effective against the bacterial infections they were developed to treat. This is because of the constant evolution of microbial pathogens in their capacity to develop or acquire resistance to current antibacterial treatments and thus survive, putting many people at risk.
Until recently, there was limited knowledge and awareness about the effects that current antibiotics exert on an individual’s own health via the collateral damage of the drug on bacteria that normally live on or in healthy humans: our microbiota. These organisms, their genes, metabolites and interactions with one another, as well as with their host collectively, represent our microbiome.
Current antibiotics disrupt the finely balanced gut microbiome, predisposing to overgrowth of resistant organisms, including multidrug-resistant pathogens. Most antibiotics currently in development are broad spectrum, and although these treatments are effective in treating disease, it is certain that their use in large scale can drive up resistance rates, leaving the health care system in a vicious circle of AMR.
A reasonable solution to combat AMR is to prioritize the development and use of extremely narrow-spectrum — ideally pathogen-specific — antibiotics that target only the primary bacterial threat while sparing the microbiome. Rapid microbiological diagnosis is key for the use of these drugs. In addition to advances in our understanding of the role of microbiome-associated biomarkers in drug development, the use of new parameters and pathways in regulatory approval and reimbursement will be key to change the antibiotic treatment paradigm.
Healio: What does the antibiotic pipeline look like right now?
Chaves: Over the past decade the early pipeline of antibiotics, especially the number of phase 1 drug candidates, has been gradually recovering and now includes a few compounds with novel mechanisms of action. On the contrary, the number of later stage compounds in phase 3 is more desolate and clearly insufficient to face the increasing global AMR threat.
In our current pipeline at Debiopharm, we are developing microbiome-sparing antibiotics within a novel class of pathogen-specific antibiotics, called FabI inhibitors. The aim of these treatments is to eliminate the pathogens from the infection sites while preserving the microbiota, with the expected benefits of preventing AMR, as well as reducing the rates of antibiotic-induced infections such as Clostridioides difficile colitis. The most advanced of these compounds, currently in phase 2, targets staphylococcal infections. A second compound, to treat gonorrhea, is expected to start phase 1 soon.
Healio: Have the major issues hindering the development of antibiotics changed in the past few years?
Chaves: The environment for developing antibiotics has been particularly challenging for a number of years. The development of new antibiotics, particularly new classes that can overcome existing resistance mechanisms, has been hindered by a failure of the health care system marketplace to adequately recognize the societal value of these products and compensate accordingly for their development.
This, together with the lengthy process of moving antibiotic candidates through the pipeline, has led to an overall reduction in pharmaceutical companies’ commitment to working on antibiotic development. On the positive side, however, in the aftermath of the COVID-19 pandemic, we have seen a heightened sense of importance emerge regarding the urgency to bolster innovation in the antimicrobial space, as well as with the need to be more adequately prepared for the threat of future pandemics, especially the possibility of a bacterial pandemic.
At Debiopharm, we have been working to address the challenges associated with antibiotic development. We have been actively seeking collaborations with innovative companies to help develop a better understanding around balancing stewardship initiatives alongside a regulatory and reimbursement model that supports the development and use of antibiotics.
Healio: What would help create a more favorable environment for the development of new antibiotics?
Chaves: There is a need to improve incentivization and funding for pharmaceutical companies to develop antibiotics, and also implement new pricing reimbursement pathways that adequately reflect the societal value of antibiotics.
In addition to the need for innovative models of reimbursement, like subscription models, companies need to build a more sustainable business model that entices biotech and pharma companies to invest in antibiotic development. We also need to define new regulatory parameters that consider the microbiome-sparing benefit for pathogen-specific therapies. New therapies not only need to be effective against the bacteria causing the illness but must also avoid the collateral damage that has been shown to exacerbate the problem of AMR.
Many AMR stakeholders are hopeful that a different type of business model, such as a subscription model, will bolster enthusiasm for antibiotic development globally. In the United States, the Pasteur Act has been reintroduced in Congress for the third time. If passed, the bill would establish a subscription model aimed at encouraging innovative antimicrobial drug development to treat drug-resistant infections. Bills such as the Pasteur Act are imperative in combating AMR and would allow countries to encourage new antibiotic development and be prepared for high threat pathogens.
References:
- Chaves R, McDonald C, et al. The public health case for microbiome-sparing antibiotics: Potential need for new pathways in regulatory approval and reimbursement. Presented at: World Anti-Microbial Resistance Congress and Disease Prevention & Control Summit; Sept. 7-8, 2023; Philadelphia.
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Healio interview.
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